MINI REVIEW
published: 25 April 2017
doi: 10.3389/fmicb.2017.00759
Host Factors Involved in the
Intracellular Movement of Bamboo
mosaic virus
Chi-Ping Cheng *
Department of Life Sciences, Tzu Chi University, Hualien, Taiwan
Edited by:
Henryk Hanokh Czosnek,
Hebrew University of Jerusalem, Israel
Reviewed by:
Vicente Pallas,
Instituto de Biología Molecular y
Celular de Plantas (CSIC-UPV), Spain
Miguel A. Aranda,
Consejo Superior de Investigaciones
Científicas (CSIC), Spain
*Correspondence:
Chi-Ping Cheng
[email protected]
Specialty section:
This article was submitted to
Virology,
a section of the journal
Frontiers in Microbiology
Received: 06 January 2017
Accepted: 12 April 2017
Published: 25 April 2017
Citation:
Cheng C-P (2017) Host Factors
Involved in the Intracellular Movement
of Bamboo mosaic virus.
Front. Microbiol. 8:759.
doi: 10.3389/fmicb.2017.00759
Viruses move intracellularly to their replication compartments, and the newly synthesized
viral complexes are transported to neighboring cells through hijacking of the host
endomembrane systems. During these processes, numerous interactions occur among
viral proteins, host proteins, and the cytoskeleton system. This review mainly focuses
on the plant endomembrane network, which may be utilized by Bamboo mosaic virus
(BaMV) to move to its replication compartment, and summarizes the host factors that
may be directly involved in delivering BaMV cargoes during intracellular movement.
Accumulating evidence indicates that plant endomembrane systems are highly similar
but exhibit significant variations from those of other eukaryotic cells. Several Nicotiana
benthamiana host proteins have recently been identified to participate in the intracellular
movement of BaMV. Chloroplast phosphoglycerate kinase, a host protein transported
to chloroplasts, binds to BaMV RNAs and facilitates BaMV replication. NbRABG3f is a
small GTPase that plays an essential role in vesicle transportation and is also involved
in BaMV replication. These two host proteins may deliver BaMV to the replication
compartment. Rab GTPase activation protein 1, which switches Rab GTPase to the
inactive conformation, participates in the cell-to-cell movement of BaMV, possibly by
trafficking BaMV cargo to neighboring cells after replication. By analyzing the host
factors involved in the intracellular movement of BaMV and the current knowledge of
plant endomembrane systems, a tentative model for BaMV transport to its replication
site within plant cells is proposed.
Keywords: Bamboo mosaic virus, intracellular movement, vesicle trafficking, endomembrane system, host
factors
INTRODUCTION
Membrane trafficking delivers materials between the endomembrane system and the plasma
membrane and therefore plays an essential role in cell survival and development (Cheung and
de Vries, 2008). Many animal microbes that reproduce intracellularly, including viruses and
bacteria, have been shown to utilize host endomembrane trafficking and the autophagy system
for intracellular transport within the host cells (Cossart and Helenius, 2014; Yamauchi and Greber,
2016), whereas other microbes alter the degradation pathway used by the host cells to destroy the
intruding pathogens (Miller and Krijnse-Locker, 2008; Mudhakir and Harashima, 2009; Yamauchi
and Greber, 2016). Rab proteins are small GTPases involved in membrane trafficking of cells,
specifically in vesicle formation and fusion. Recent studies of Salmonella enterica Typhimurium,
Frontiers in Microbiology | www.frontiersin.org
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Intracellular Movement of Bamboo mosaic virus
replication sites within the host cells remain largely unknown.
Particularly, the endomembrane trafficking systems in plants
seem to be more complicated and have not been completely
revealed (Saito and Ueda, 2009; Uemura, 2016). Moreover,
studies of the intracellular movement of plant viruses have mostly
focused on cell-to-cell movement through the plasmodesmata;
these intracellular movement pathways of plant viruses have been
reviewed in several articles (Park et al., 2014; Heinlein, 2015; Liou
et al., 2015). Host factors participating in membrane trafficking
or protein targeting may play roles in delivering BaMV or its
cargoes to the replication sites. Based on the current knowledge
of intracellular trafficking pathways in plants, a model for the
intracellular movement of BaMV to its replication compartment
is proposed. After replication, plant viruses travel intracellularly
to reach plasmodesmata for cell-to-cell movement. A vesicle
trafficking-related host protein participates in BaMV cell-to-cell
movement; its potential role in BaMV intracellular movement is
also discussed in this review.
an animal pathogenic bacterium, have identified several bacterial
effectors that target various Rab proteins for replication within
the host cells (Spano et al., 2011, 2016; McGourty et al., 2012;
D’Costa et al., 2015).
Many plant viruses induce membrane remodeling after
infecting their host cells. Studies focusing on the modification
of endomembrane systems induced by plant viruses have
substantially improved our understanding of the intracellular
movement of plant viruses. Membrane targeting or recruitment
by viral proteins in the viral replication compartment is
often the cause of endomembrane remodeling, as has been
demonstrated for many viruses (Wei et al., 2010, 2013; Hyodo
et al., 2014; Xu and Nagy, 2014). Grapevine fanleaf nepovirus
(GFLV) infection induces structural changes in the endoplasmic
reticulum (ER) membranes to allow virus replication in the
ER-derived membrane. Although host factors have not been
identified, inhibitor treatment has demonstrated that vesicle
transport between Golgi and ER is essential for GFLV replication
(Ritzenthaler et al., 2002; Fuchs et al., 2017). A study on
plant potyviruses revealed that the 6k2 viral protein of Turnip
mosaic virus (TuMV) induces the formation of vesicles derived
from ER and targets them to the chloroplasts for replication
(Wei et al., 2010). Melon necrotic spot virus (MNSV) has been
shown to replicate in mitochondria, which is significantly altered
by the virus-encoded p29 protein targeting the mitochondria
membrane (Mochizuki et al., 2009; Gomez-Aix et al., 2015).
ER disorder has also been observed, and the p7B movement
protein of MNSV is localized to ER, Golgi, actin filaments,
and plasmodesmata. Disruption of the transport between ER
and Golgi results in the accumulation of p7B within the ER.
Therefore, the ER-to-Golgi secretory pathway could be involved
in the intra- and intercellular movement of MNSV (Genoves
et al., 2010).
In addition to the viral encoded proteins, host factors are
also involved in the membrane remodeling process. Using yeast
as a model system and by performing further testing in host
plants, several studies on Tomato bushy stunt virus (TBSV) have
demonstrated that host factors are responsible for delivering
components to remodel the membrane-associated compartment
for viral replication (Barajas et al., 2014; Xu and Nagy, 2016).
Heat shock protein 70 is associated with the replication complex
of TBSV and facilitates the insertion of viral replication proteins
into the yeast membrane (Wang et al., 2009). The GTP-bound
active form of Rab5-positive endosome is hijacked by TBSV for
enrichment of phosphatidylethanolamine at the replication site
(Xu and Nagy, 2016). A host SNARE protein, Syp71, mediates
the fusion between the TuMV-induced vesicles and chloroplasts,
which is required for TuMV infection (Wei et al., 2013). In
yeast, membrane-shaping reticulon homology domain proteins
are crucial for the formation of the replication compartment
induced by the Brome mosaic virus (BMV) 1a protein (Diaz et al.,
2010). These findings indicate that membrane trafficking and
targeting are essential processes for plant virus replication.
Several pathways of intracellular movement have been
proposed for animal viruses after they enter the host cells
(Mudhakir and Harashima, 2009). By contrast, the trafficking
pathways for the intracellular movement of plant viruses to their
Frontiers in Microbiology | www.frontiersin.org
POSSIBLE REPLICATION
COMPARTMENTS FOR BaMV
Virus infection commonly induces the formation of dynamic
membrane-associated structures that are associated to the virus
replication and movement (Grangeon et al., 2012; Heinlein,
2015). Chloroplasts are one of the types of compartments suitable
for plant virus replication (Wei et al., 2010; Zhao et al., 2016).
Using BaMV 30 RNA as a probe for in situ hybridization
through electronic microscopy, BaMV viral RNAs were detected
within several organelles of green bamboo leaf cells, including
chloroplasts, mitochondria, and nuclei (Lin et al., 1993). Phage
MS2 coat protein can specifically bind to its own RNA sequence,
and viral genomic RNA engineered to contain the MS2 sequence
can be traced within the cells through the binding of GFPfused MS2 coat protein (Zhang and Simon, 2003). Recently,
through confocal microscopy, BaMV viral RNA expressing the
phage MS2 coat protein binding sequence was found to localize
within chloroplasts. Furthermore, negative-strand BaMV RNA
was found in the isolated chloroplasts, demonstrating that
chloroplasts may be among the BaMV replication compartments
within the host cells (Cheng et al., 2013a).
In contrast, Potato virus X (PVX), another potexvirus, has
been found to replicate in the ER membrane (Doronin and
Hemenway, 1996; Park et al., 2014); in addition, TGB2/3
has recently been shown to remodel the ER membrane
at plasmodesmata, where PVX coupled the replication and
movement to the neighboring cells (Tilsner et al., 2013).
HOST FACTORS PROBABLY INVOLVED
IN THE INTRACELLULAR TARGETING
OF BaMV TO THE REPLICATION
COMPARTMENT
After entering the host cells, similar to other viruses, BaMV
must travel to its replication site intracellularly. Recently, several
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Intracellular Movement of Bamboo mosaic virus
replication compartments rather than the degradation pathway
(Patarroyo et al., 2012; Dong and Levine, 2013). According to the
finding that NbRABG3f is derived from the Golgi compartment
(Huang et al., 2016) and that chloroplasts are likely to be the
replication sites of BaMV (Lin et al., 1993; Cheng et al., 2013a),
BaMV may utilize NbRABG3f or NbRABG3f-associated vesicles
for transport to chloroplasts. However, the acceptor membrane
of NbRABG3f has not yet been identified. Knowledge of the
destination of NbRABG3f in the endomembrane systems will
verify whether BaMV hijacks NbRABG3f and redirects its route
or instead utilizes NbRABG3f-associated vesicle and follows
its pathway. Further investigation of the interaction of BaMV
with NbRABG3f and other Rab proteins and further evaluation
of the colocalization of BaMV and various marker proteins
involved in endomembrane trafficking will reveal the intracellular
transportation pathway for BaMV.
host factors involved in BaMV replication have been identified
through copurification with the BaMV replicase complex (Cheng
et al., 2009; Prasanth et al., 2011; Huang et al., 2012; Lee et al.,
2015), binding to the viral RNAs (Lin et al., 2007; Cheng et al.,
2013a), and cDNA-amplified fragment length polymorphism
(cDNA-AFLP) analysis (Chen et al., 2013; Huang et al., 2013,
2016). Among these host factors, three are possibly involved in
the transportation of BaMV or its related cargoes within host
cells. Chloroplast phosphoglycerate kinase (chl-PGK) (Lin et al.,
2007; Cheng et al., 2013a) and NbRABG3f (Huang et al., 2016) are
related to BaMV replication, whereas NbRabGAP1 is essential for
the intercellular movement of BaMV (Huang et al., 2013).
In Nicotiana benthamiana, chl-PGK, a nuclear-encoded
chloroplast protein, was found to bind to the 30 untranslated
region (30 UTR) of BaMV genomic RNAs (Lin et al., 2007).
Knocking down the expression or mistargeting of chl-PGK
reduced BaMV accumulation in N. benthamiana protoplasts,
indicating that chl-PGK participates in BaMV replication (Cheng
et al., 2013a). Redirecting a BaMV RNA binding protein, EF1a,
to chloroplasts rescued the reduction of BaMV caused by the
knock-down of chl-PGK. These results demonstrate that chlPGK likely assists in the targeting of BaMV to the chloroplasts
for replication (Cheng et al., 2013a). Recently, a chl-PGK from
Arabidopsis thaliana was identified as a requirement for efficient
Watermelon mosaic virus (WMV) (Ouibrahim et al., 2014) and
Plum pox virus (Poque et al., 2015) infection. Although the
replication compartment of WMV is unknown, the 6K protein
of other potyviruses induces the formation of mobile vesicles and
transports the viruses from the ER to the chloroplast membrane
for viral replication (Wei et al., 2010). Therefore, chl-PGK may be
involved in the intracellular transport of different plant viruses to
the chloroplasts for replication.
A recent study identified that NbRABG3f, a Rab small GTPase,
is involved in BaMV replication (Huang et al., 2016). Rab small
GTPases are involved in vesicle trafficking within cells. Rab
proteins alternate between a GTP-bound active form and GDPbound inactive form, and this switching is accelerated by their
regulatory proteins (Cherfils and Zeghouf, 2013). GTP-bound
Rab proteins bud from the donor compartment and fuse with
the acceptor compartment, where GTP is hydrolyzed by GTPaseactivating proteins (GAPs) (Cherfils and Zeghouf, 2013). Based
on sequence comparison, NbRABG3f is homologous to animal
cell Rab7 protein and to A. thaliana RabG3f (Huang et al., 2016).
cDNA-AFLP analysis revealed that NbRABG3f expression was
upregulated after BaMV inoculation (Cheng et al., 2010). The
GDP-bound form of Rab GTPase can be used to trace the donor
compartment of Rab proteins (Sieczkarski and Whittaker, 2002);
thus, confocal microscopy revealed that the GDP-bound form
mutant of NbRABG3f was localized to the Golgi compartment
(Huang et al., 2016). In plant endomembrane trafficking systems,
endocytotic materials are transferred to the trans-Golgi network
for further sorting (Zhuang et al., 2015). As a plant defense
mechanism pathway, intruding pathogens are likely delivered
to the multi-vesicular body (MVE)/prevacuolar compartment
(PVC), or autophagosome and then delivered to the vacuoles
for degradation (Teh and Hofius, 2014). Successful pathogen
infection results from a redirection of the pathway to their
Frontiers in Microbiology | www.frontiersin.org
POSSIBLE MODEL FOR BaMV
INTRACELLULAR MOVEMENT TO ITS
REPLICATION COMPARTMENT
In uninfected N. benthamiana cells, NbRABG3f and its
associated vesicles are generated by the Golgi compartment
(Huang et al., 2016). The destination of NbRABG3f is
currently unknown. According to a putative model proposed
for Arabidopsis, the endocytosed materials can be (1) delivered
to the MVE/PVC, or autophagosome and then transported to
the vacuoles for degradation, or (2) recycled into the plasma
membrane (Uemura, 2016; Vukasinovic and Zarsky, 2016).
A previous study demonstrated that Arabidopsis AtRABG3f
mediates transport from PVC to the vacuole (Cui et al., 2014).
Although the donor membrane of NbRABG3f is different
from that of AtRABG3f, possibly because of variation in
the C-terminal sequence, based on the fact that NbRABG3f
is highly homologous to AtRABG3f (Huang et al., 2016),
NbRABG3f likely participates in the transport of vesicles to
other endomembrane systems rather than in their delivery to the
recycling pathway.
According to current knowledge of the intracellular trafficking
pathways in plants and studies of NbRABG3f and chl-PGK,
BaMV may utilize NbRABG3f-associated vesicles for vesicle
trafficking. During vesicle trafficking, chl-PGK is recruited and
assists in the targeting of the BaMV complex to the chloroplasts,
which are one of the types of BaMV replication compartments
(Cheng et al., 2013a) (Figure 1, upper). By contrast, similar to
the role of Rab5 protein in TBSV replication (Xu and Nagy,
2016), NbRABG3f may deliver the materials required for BaMV
replication to the chloroplasts, and chl-PGK may bind BaMV
RNA and direct the BaMV complex to the chloroplast for
replication (Figure 1, lower).
Although the transportation pathway for chloroplasttargeting proteins to the chloroplast is not completely clear,
to date, several pathways have been proposed for proteins
transported to the chloroplasts after translation (Radhamony
and Theg, 2006; Shi and Theg, 2013). Most chloroplast proteins
contain an N-terminal cleavable transit peptide that mediates the
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Intracellular Movement of Bamboo mosaic virus
FIGURE 1 | A possible model for BaMV intracellular movement to the chloroplasts. In the normal membrane-trafficking pathway, NbRABG3f-associated
vesicles bud from Golgi compartment. There are two possible pathways that NbRABG3f and chl-PGK may participate in delivering of BaMV cargoes to the
chloroplasts. (1) When BaMV infects the cells, it may hijack the NbRABG3f-associated vesicles and redirect the vesicles to the chloroplast which is one of its
replication compartments. During the transportation to the chloroplasts, chl-PGK is recruited to the BaMV complex and targets BaMV complex to the chloroplasts
stroma (Upper). (2) Alternatively, NbRABG3f-associated vesicles may deliver materials required for BaMV replication to the chloroplasts and chl-PGK binds to BaMV
viral RNA and targets it to the chloroplast stroma for replication (Lower).
a Rab-GTPase activation protein, has been identified through
cDNA-AFLP analysis, and its expression is upregulated after
BaMV inoculation (Huang et al., 2013). RabGAP contains the
TBC (Tre2/Bub2/Cdc16) catalytic domain that can promote
GTP hydrolysis and thus inactivates Rab proteins (Frasa et al.,
2012). Rab proteins participate in the regulation of vesicle
formation and trafficking in the endomembrane system. In the
study of NbRabGAP1, low NbRabGAP1 expression reduced
BaMV accumulation in N. benthamiana leaves, but not in
protoplasts, whereas overexpression of NbRabGAP1 exerted the
opposite effect. Based on these results, it is hypothesized that
NbRabGAP1 is involved in the delivery of the BaMV/BaMVrelated cargo from the virus replication complex to neighboring
cells (Huang et al., 2013; Liou et al., 2015). An attempt to
examine the interaction between NbRabGAP1 and NbRABG3f
was unsuccessful (unpublished data). This outcome was expected
because NbRabG3f participates in BaMV replication, whereas
NbRabGAP1 assists in the intercellular movement of BaMV.
Similar to PVX, the BaMV movement proteins TGBp2 and
TGBp3 are ER-targeting membrane proteins (Hsu et al., 2008).
The BaMV infectious complex has been proposed to move
from perinuclear ER-derived membrane-bound bodies (MBB)
to the plasmodesmata (Wu et al., 2011; Liou et al., 2015).
After BaMV replication, NbRabGAP1 possibly participates in
the delivery of BaMV cargoes with an unknown Rab protein
toward the plasmodesmata through ER and post-ER secretory
pathways. Alternatively, NbRabGAP1 may recycle the BaMV
movement proteins from plasmodesmata to assist in the next
round of BaMV transportation (Huang et al., 2013). However,
the connection between chloroplasts and the MBB requires
further investigation to unveil the intracellular route after BaMV
replication.
targeting of the protein to the chloroplasts (Shi and Theg, 2013).
N. benthamiana chl-PGK also contains a putative N-terminal
transit peptide (Cheng et al., 2013a), indicating that it can be
transported from the ER to the chloroplast stroma, and that such
transport is directed by the N-terminal transit peptide. Whether
chl-PGK is recruited to the NbRABG3f-associated vesicle or
these two host proteins are involved in separate steps of BaMV
transportation is an interesting question that remains to be
explored. Future studies should investigate whether chl-PGK
interacts with NbRABG3f or NbRABG3f-associated vesicles
during the transportation process.
A HOST FACTOR POSSIBLY INVOLVED
IN BaMV VESICLE TRAFFICKING TO THE
PLASMODESMATA FOR
INTERCELLULAR MOVEMENT
After the replication of plant viruses, virion or virus
ribonucleoprotein (vRNP) facilitates their intercellular
movement through the plasmodesmata. Unlike PVX, which
moves intercellularly as vRNP, BaMV is likely to move as a virion
associated with TGBp2 and TGBp3-based ER membrane (Chou
et al., 2013). Several BaMV viral proteins and N. benthamiana
host factors have been demonstrated to facilitate the intercellular
movement, but not the replication, of BaMV (Cheng et al.,
2013b; Huang et al., 2013; Hung et al., 2014). A recent, thorough
review of the intercellular movement of BaMV hypothesizes the
possible roles of the viral and host proteins in the intercellular
movement of BaMV (Liou et al., 2015). Among the host proteins
involved in the intercellular movement of BaMV, NbRabGAP1,
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Studies in PVX have indicated that its TGB2/3 movement
proteins induce ER-derived granular vesicles, which are essential
for PVX cell-to-cell movement (Ju et al., 2007); therefore,
the PVX movement complex may be transported through
these vesicles to plasmodesmata (Verchot-Lubicz et al., 2010).
Accordingly, as yet unidentified host factors may be present that
function as Rab or RabGAP proteins to facilitate PVX movement.
The kinases CK2 and NbSTKL are other host factors also
involved in the cell-to-cell movement of BaMV (Cheng et al.,
2013b; Hung et al., 2014). Knowledge on host factors that affect
the intercellular movement of potexviruses have been reviewed
recently (Park et al., 2014; Liou et al., 2015). Their functions in
assisting BaMV or other potexvirus movement have also been
discussed in a recent review, which reported that they might not
directly participate in the transportation of BaMV cargoes (Liou
et al., 2015). Therefore, they are not included in this review.
chloroplast-targeting protein, and its targeting ability is required
for BaMV replication. Therefore, NbRABG3f and chl-PGK may
play roles in delivering BaMV and its related complex to
chloroplasts, which are a type of BaMV replication compartment.
After completing replication, BaMV cargoes are delivered to
the plasmodesmata for intercellular movement. NbRabGAP1,
a Rab-associated protein, is not involved in BaMV replication
but participates in its intercellular movement. Accordingly,
NbRabGAP1 may be involved in the intracellular transport of the
BaMV complex to the plasmodesmata after BaMV replication.
Additional studies on dissecting the co-localization or interaction
between BaMV and other vesicle proteins are required to clarify
the intracellular movement pathway for BaMV.
AUTHOR CONTRIBUTIONS
C-PC wrote and edited the paper.
SUMMARY
FUNDING
In this review, I summarized the host factors that participate in
membrane trafficking and a specific chloroplast targeting protein
that may participate in BaMV transportation within the cells.
A possible model was proposed to demonstrate how BaMV
is delivered to its replication compartment. One of the host
factors, NbRABG3f, is a small GTPase that mediates vesicle
trafficking and is derived from the Golgi compartment. Both
GTPase activity and membrane-targeting ability are essential
for BaMV replication. Another host protein, chl-PGK, is a
This work was financially supported by MOST (grant number
MOST 104-2313-B-320-001 and MOST 105-2313-B-320-001).
ACKNOWLEDGMENT
The author acknowledges Ms. Pei-Yu Hou for her contribution
to the figure.
REFERENCES
Chou, Y. L., Hung, Y. J., Tseng, Y. H., Hsu, H. T., Yang, J. Y., Wung, C. H.,
et al. (2013). The stable association of virion with the triple-gene-block protein
3-based complex of Bamboo mosaic virus. PLoS Pathog. 9:e1003405. doi: 10.
1371/journal.ppat.1003405
Cossart, P., and Helenius, A. (2014). Endocytosis of viruses and bacteria. Cold
Spring Harb. Perspect. Biol. 6:a016972. doi: 10.1101/cshperspect.a016972
Cui, Y., Zhao, Q., Gao, C., Ding, Y., Zeng, Y., Ueda, T., et al. (2014). Activation
of the Rab7 GTPase by the MON1-CCZ1 complex is essential for PVC-tovacuole trafficking and plant growth in Arabidopsis. Plant Cell 26, 2080–2097.
doi: 10.1105/tpc.114.123141
D’Costa, V. M., Braun, V., Landekic, M., Shi, R., Proteau, A., McDonald, L.,
et al. (2015). Salmonella disrupts host endocytic trafficking by SopD2-mediated
inhibition of Rab7. Cell Rep. 12, 1508–1518. doi: 10.1016/j.celrep.2015.07.063
Diaz, A., Wang, X., and Ahlquist, P. (2010). Membrane-shaping host reticulon
proteins play crucial roles in viral RNA replication compartment formation
and function. Proc. Natl. Acad. Sci. U.S.A. 107, 16291–16296. doi: 10.1073/pnas.
1011105107
Dong, X., and Levine, B. (2013). Autophagy and viruses: adversaries or allies?
J. Innate Immun. 5, 480–493. doi: 10.1159/000346388
Doronin, S. V., and Hemenway, C. (1996). Synthesis of potato virus X RNAs by
membrane-containing extracts. J. Virol. 70, 4795–4799.
Frasa, M. A., Koessmeier, K. T., Ahmadian, M. R., and Braga, V. M. (2012).
Illuminating the functional and structural repertoire of human TBC/RABGAPs.
Nat. Rev. Mol. Cell Biol. 13, 67–73. doi: 10.1038/nrm3267
Fuchs, M., Schmitt-Keichinger, C., and Sanfacon, H. (2017). A renaissance in
nepovirus research provides new insights into their molecular interface with
hosts and vectors. Adv. Virus Res. 97, 61–105. doi: 10.1016/bs.aivir.2016.08.009
Genoves, A., Navarro, J. A., and Pallas, V. (2010). The Intra- and intercellular
movement of Melon necrotic spot virus (MNSV) depends on an active secretory
pathway. Mol. Plant Microbe Interact. 23, 263–272. doi: 10.1094/MPMI-23-30263
Barajas, D., Xu, K., de Castro Martin, I. F., Sasvari, Z., Brandizzi, F., Risco, C.,
et al. (2014). Co-opted oxysterol-binding ORP and VAP proteins channel
sterols to RNA virus replication sites via membrane contact sites. PLoS Pathog.
10:e1004388. doi: 10.1371/journal.ppat.1004388
Chen, I. H., Chiu, M. H., Cheng, S. F., Hsu, Y. H., and Tsai, C. H. (2013).
The glutathione transferase of Nicotiana benthamiana NbGSTU4 plays a role
in regulating the early replication of Bamboo mosaic virus. New Phytol. 199,
749–757. doi: 10.1111/nph.12304
Cheng, C. W., Hsiao, Y. Y., Wu, H. C., Chuang, C. M., Chen, J. S., Tsai,
C. H., et al. (2009). Suppression of Bamboo mosaic virus accumulation by a
putative methyltransferase in Nicotiana benthamiana. J. Virol. 83, 5796–5805.
doi: 10.1128/JVI.02471-08
Cheng, S. F., Huang, Y. P., Chen, L. H., Hsu, Y. H., and Tsai, C. H. (2013a).
Chloroplast phosphoglycerate kinase is involved in the targeting of Bamboo
mosaic virus to chloroplasts in Nicotiana benthamiana plants. Plant Physiol. 163,
1598–1608. doi: 10.1104/pp.113.229666
Cheng, S. F., Huang, Y. P., Wu, Z. R., Hu, C. C., Hsu, Y. H., and Tsai, C. H.
(2010). Identification of differentially expressed genes induced by Bamboo
mosaic virus infection in Nicotiana benthamiana by cDNA-amplified fragment
length polymorphism. BMC Plant Biol. 10:286. doi: 10.1186/1471-2229-10-286
Cheng, S. F., Tsai, M. S., Huang, C. L., Huang, Y. P., Chen, I. H., Lin, N. S.,
et al. (2013b). Ser/Thr kinase-like protein of Nicotiana benthamiana is involved
in the cell-to-cell movement of Bamboo mosaic virus. PLoS ONE 8:e62907.
doi: 10.1371/journal.pone.0062907
Cherfils, J., and Zeghouf, M. (2013). Regulation of small GTPases by GEFs, GAPs,
and GDIs. Physiol. Rev. 93, 269–309. doi: 10.1152/physrev.00003.2012
Cheung, A. Y., and de Vries, S. C. (2008). Membrane trafficking: intracellular
highways and country roads. Plant Physiol. 147, 1451–1453. doi: 10.1104/pp.
104.900266
Frontiers in Microbiology | www.frontiersin.org
5
April 2017 | Volume 8 | Article 759
Cheng
Intracellular Movement of Bamboo mosaic virus
Gomez-Aix, C., Garcia-Garcia, M., Aranda, M. A., and Sanchez-Pina, M. A.
(2015). Melon necrotic spot virus replication occurs in association with altered
mitochondria. Mol. Plant Microbe Interact. 28, 387–397. doi: 10.1094/MPMI09-14-0274-R
Grangeon, R., Jiang, J., and Laliberte, J. F. (2012). Host endomembrane recruitment
for plant RNA virus replication. Curr. Opin. Virol. 2, 683–690. doi: 10.1016/j.
coviro.2012.10.003
Heinlein, M. (2015). Plant virus replication and movement. Virology 47, 657–671.
doi: 10.1016/j.virol.2015.01.025
Hsu, H. T., Chou, Y. L., Tseng, Y. H., Lin, Y. H., Lin, T. M., Lin, N. S., et al. (2008).
Topological properties of the triple gene block protein 2 of Bamboo mosaic
virus. Virology 379, 1–9. doi: 10.1016/j.virol.2008.06.019
Huang, Y. P., Chen, J. S., Hsu, Y. H., and Tsai, C. H. (2013). A putative Rab-GTPase
activation protein from Nicotiana benthamiana is important for Bamboo mosaic
virus intercellular movement. Virology 447, 292–299. doi: 10.1016/j.virol.2013.
09.021
Huang, Y. P., Jhuo, J. H., Tsai, M. S., Tsai, C. H., Chen, H. C., Lin, N. S., et al.
(2016). NbRABG3f, a member of Rab GTPase, is involved in Bamboo mosaic
virus infection in Nicotiana benthamiana. Mol. Plant Pathol. 17, 714–726.
doi: 10.1111/mpp.12325
Huang, Y. W., Hu, C. C., Liou, M. R., Chang, B. Y., Tsai, C. H., Meng, M., et al.
(2012). Hsp90 interacts specifically with viral RNA and differentially regulates
replication initiation of Bamboo mosaic virus and associated satellite RNA. PLoS
Pathog. 8:e1002726. doi: 10.1371/journal.ppat.1002726
Hung, C. J., Huang, Y. W., Liou, M. R., Lee, Y. C., Lin, N. S., Meng, M., et al.
(2014). Phosphorylation of coat protein by protein kinase CK2 regulates cellto-cell movement of Bamboo mosaic virus through modulating RNA binding.
Mol. Plant Microbe Interact. 27, 1211–1225. doi: 10.1094/MPMI-04-14-0112-R
Hyodo, K., Kaido, M., and Okuno, T. (2014). Host and viral RNA-binding proteins
involved in membrane targeting, replication and intercellular movement of
plant RNA virus genomes. Front. Plant Sci. 5:321. doi: 10.3389/fpls.2014.00321
Ju, H. J., Brown, J. E., Ye, C. M., and Verchot-Lubicz, J. (2007). Mutations in the
central domain of potato virus X TGBp2 eliminate granular vesicles and virus
cell-to-cell trafficking. J. Virol. 81, 1899–1911. doi: 10.1128/JVI.02009-06
Lee, C. C., Lin, T. L., Lin, J. W., Han, Y. T., Huang, Y. T., Hsu, Y. H., et al. (2015).
Promotion of Bamboo Mosaic Virus accumulation in Nicotiana benthamiana
by 5’–>3’ Exonuclease NbXRN4. Front. Microbiol. 6:1508. doi: 10.3389/fmicb.
2015.01508
Lin, J. W., Ding, M. P., Hsu, Y. H., and Tsai, C. H. (2007). Chloroplast
phosphoglycerate kinase, a gluconeogenetic enzyme, is required for efficient
accumulation of Bamboo mosaic virus. Nucleic Acids Res. 35, 424–432. doi:
10.1093/nar/gkl1061
Lin, N. S., Chen, C. C., and Hsu, Y. H. (1993). Post-embedding in situ hybridization
for localization of viral nucleic acid in ultra-thin sections. J. Histochem.
Cytochem. 41, 1513–1519.
Liou, M. R., Hu, C. C., Chou, Y. L., Chang, B. Y., Lin, N. S., and Hsu, Y. H. (2015).
Viral elements and host cellular proteins in intercellular movement of Bamboo
mosaic virus. Curr. Opin. Virol. 12, 99–108. doi: 10.1016/j.coviro.2015.04.005
McGourty, K., Thurston, T. L., Matthews, S. A., Pinaud, L., Mota, L. J.,
and Holden, D. W. (2012). Salmonella inhibits retrograde trafficking of
mannose-6-phosphate receptors and lysosome function. Science 338, 963–967.
doi: 10.1126/science.1227037
Miller, S., and Krijnse-Locker, J. (2008). Modification of intracellular membrane
structures for virus replication. Nat. Rev. Microbiol. 6, 363–374. doi: 10.1038/
nrmicro1890
Mochizuki, T., Hirai, K., Kanda, A., Ohnishi, J., Ohki, T., and Tsuda, S. (2009).
Induction of necrosis via mitochondrial targeting of Melon necrotic spot virus
replication protein p29 by its second transmembrane domain. Virology 390,
239–249. doi: 10.1016/j.virol.2009.05.012
Mudhakir, D., and Harashima, H. (2009). Learning from the viral journey: how
to enter cells and how to overcome intracellular barriers to reach the nucleus.
AAPS J. 11, 65–77. doi: 10.1208/s12248-009-9080-9
Ouibrahim, L., Mazier, M., Estevan, J., Pagny, G., Decroocq, V., Desbiez, C., et al.
(2014). Cloning of the Arabidopsis rwm1 gene for resistance to Watermelon
mosaic virus points to a new function for natural virus resistance genes. Plant J.
79, 705–716. doi: 10.1111/tpj.12586
Frontiers in Microbiology | www.frontiersin.org
Park, M. R., Jeong, R. D., and Kim, K. H. (2014). Understanding the intracellular
trafficking and intercellular transport of potexviruses in their host plants. Front.
Plant Sci. 5:60. doi: 10.3389/fpls.2014.00060
Patarroyo, C., Laliberte, J. F., and Zheng, H. (2012). Hijack it, change it: how do
plant viruses utilize the host secretory pathway for efficient viral replication and
spread? Front. Plant Sci. 3:308. doi: 10.3389/fpls.2012.00308
Poque, S., Pagny, G., Ouibrahim, L., Chague, A., Eyquard, J. P., Caballero, M.,
et al. (2015). Allelic variation at the rpv1 locus controls partial resistance to
Plum pox virus infection in Arabidopsis thaliana. BMC Plant Biol. 15:159.
doi: 10.1186/s12870-015-0559-5
Prasanth, K. R., Huang, Y. W., Liou, M. R., Wang, R. Y., Hu, C. C., Tsai, C. H.,
et al. (2011). Glyceraldehyde 3-phosphate dehydrogenase negatively regulates
the replication of Bamboo mosaic virus and its associated satellite RNA. J. Virol.
85, 8829–8840. doi: 10.1128/JVI.00556-11
Radhamony, R. N., and Theg, S. M. (2006). Evidence for an ER to Golgi
to chloroplast protein transport pathway. Trends Cell Biol. 16, 385–387.
doi: 10.1016/j.tcb.2006.06.003
Ritzenthaler, C., Laporte, C., Gaire, F., Dunoyer, P., Schmitt, C., Duval, S., et al.
(2002). Grapevine fanleaf virus replication occurs on endoplasmic reticulumderived membranes. J. Virol. 76, 8808–8819.
Saito, C., and Ueda, T. (2009). Chapter 4: functions of RAB and SNARE proteins
in plant life. Int. Rev. Cell Mol. Biol. 274, 183–233. doi: 10.1016/S1937-6448(08)
02004-2
Shi, L. X., and Theg, S. M. (2013). The chloroplast protein import system: from
algae to trees. Biochim. Biophys. Acta 1833, 314–331. doi: 10.1016/j.bbamcr.
2012.10.002
Sieczkarski, S. B., and Whittaker, G. R. (2002). Dissecting virus entry via
endocytosis. J. Gen. Virol. 83(Pt 7), 1535–1545. doi: 10.1099/0022-1317-83-71535
Spano, S., Gao, X., Hannemann, S., Lara-Tejero, M., and Galan, J. E. (2016).
A bacterial pathogen targets a host rab-family GTPase defense pathway with
a GAP. Cell Host Microbe 19, 216–226. doi: 10.1016/j.chom.2016.01.004
Spano, S., Liu, X., and Galan, J. E. (2011). Proteolytic targeting of Rab29 by
an effector protein distinguishes the intracellular compartments of humanadapted and broad-host Salmonella. Proc. Natl. Acad. Sci. U.S.A. 108, 18418–
18423. doi: 10.1073/pnas.1111959108
Teh, O. K., and Hofius, D. (2014). Membrane trafficking and autophagy in
pathogen-triggered cell death and immunity. J. Exp. Bot. 65, 1297–1312.
doi: 10.1093/jxb/ert441
Tilsner, J., Linnik, O., Louveaux, M., Roberts, I. M., Chapman, S. N., and Oparka,
K. J. (2013). Replication and trafficking of a plant virus are coupled at the
entrances of plasmodesmata. J. Cell Biol. 201, 981–995. doi: 10.1083/jcb.
201304003
Uemura, T. (2016). Physiological roles of plant post-golgi transport pathways
in membrane trafficking. Plant Cell Physiol. 57, 2013–2019. doi: 10.1093/pcp/
pcw149
Verchot-Lubicz, J., Torrance, L., Solovyev, A. G., Morozov, S. Y., Jackson,
A. O., and Gilmer, D. (2010). Varied movement strategies employed by triple
gene block-encoding viruses. Mol. Plant Microbe Interact. 23, 1231–1247.
doi: 10.1094/MPMI-04-10-0086
Vukasinovic, N., and Zarsky, V. (2016). Tethering complexes in the Arabidopsis
endomembrane System. Front. Cell Dev. Biol. 4:46. doi: 10.3389/fcell.2016.
00046
Wang, R. Y., Stork, J., and Nagy, P. D. (2009). A key role for heat shock protein
70 in the localization and insertion of tombusvirus replication proteins to
intracellular membranes. J. Virol. 83, 3276–3287. doi: 10.1128/JVI.02313-08
Wei, T., Huang, T. S., McNeil, J., Laliberte, J. F., Hong, J., Nelson, R. S., et al. (2010).
Sequential recruitment of the endoplasmic reticulum and chloroplasts for plant
potyvirus replication. J. Virol. 84, 799–809. doi: 10.1128/JVI.01824-09
Wei, T., Zhang, C., Hou, X., Sanfacon, H., and Wang, A. (2013). The SNARE
protein Syp71 is essential for turnip mosaic virus infection by mediating
fusion of virus-induced vesicles with chloroplasts. PLoS Pathog. 9:e1003378.
doi: 10.1371/journal.ppat.1003378
Wu, C. H., Lee, S. C., and Wang, C. W. (2011). Viral protein targeting to the cortical
endoplasmic reticulum is required for cell-cell spreading in plants. J. Cell Biol.
193, 521–535. doi: 10.1083/jcb.201006023
6
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Cheng
Intracellular Movement of Bamboo mosaic virus
Xu, K., and Nagy, P. D. (2014). Expanding use of multi-origin subcellular
membranes by positive-strand RNA viruses during replication. Curr. Opin.
Virol. 9, 119–126. doi: 10.1016/j.coviro.2014.09.015
Xu, K., and Nagy, P. D. (2016). Enrichment of Phosphatidylethanolamine in viral
replication compartments via Co-opting the Endosomal Rab5 small GTPase by
a positive-strand RNA Virus. PLoS Biol. 14:e2000128. doi: 10.1371/journal.pbio.
2000128
Yamauchi, Y., and Greber, U. F. (2016). Principles of Virus Uncoating: cues and the
Snooker Ball. Traffic 17, 569–592. doi: 10.1111/tra.12387
Zhang, F., and Simon, A. E. (2003). A novel procedure for the localization of viral
RNAs in protoplasts and whole plants. Plant J. 35, 665–673.
Zhao, J., Zhang, X., Hong, Y., and Liu, Y. (2016). Chloroplast in plantvirus interaction. Front. Microbiol. 7:1565. doi: 10.3389/fmicb.2016.
01565
Frontiers in Microbiology | www.frontiersin.org
Zhuang, X., Cui, Y., Gao, C., and Jiang, L. (2015). Endocytic and autophagic
pathways crosstalk in plants. Curr. Opin. Plant Biol. 28, 39–47. doi: 10.1016/
j.pbi.2015.08.010
Conflict of Interest Statement: The author declares that the research was
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